MSG (E621): Could a Common Flavor Enhancer Be Behind Headaches, Gut Discomfort and Skin Reactions?
- Marcelline Goyen
- Jan 22
- 4 min read
Table of contents
Introduction MSG (E621), gut and skin
My personal recent experience with MSG (E621), gut and skin: for a few days, I'd had a nagging headache and a bit sensitive gut, even though there seemed to be no apparent cause, such as stress. I also suddenly developed skin reactions: a few small, painful bumps on my neck that I normally never get. Just to be sure, I checked my diet: I'd been eating a handful of Indonesian ketjang pedis cocktail nuts every evening for a week. The packaging now showed that it contained E621, just like the Japanese tuna salad I'd been spreading on my bread for a week. I'd noticed before that I react quite strongly to MSG, or Ve-tsin, or E621, and I normally pay close attention to packaging to avoid this E number. But this time, I was caught in it again. So, I wanted to write a blog post about it so others can become aware of it too.
MSG or E621
Monosodium glutamate — better known as MSG or E621 — is a widely used flavor enhancer found in many everyday foods, from savory snacks and sauces to ready-made salads and spreads. Regulatory authorities such as the EFSA and FDA consider MSG safe within established intake limits. Yet, emerging research suggests that for some individuals, MSG may not be as harmless as once thought.
A growing body of scientific literature is now exploring how MSG can influence the gut, nervous system and immune responses, potentially explaining symptoms such as headaches, digestive complaints and even skin reactions in sensitive people. PMC+1
MSG and the Gut Microbiome
A recent systematic review published on PubMed Central examined the effects of MSG on the body, with a particular focus on the gut microbiota. The authors report that MSG intake can alter the composition of gut bacteria, especially in animal and preclinical studies. These shifts may affect intestinal permeability, immune regulation and metabolic pathways. PMC
Although most of this evidence comes from experimental models, it raises important questions about how long-term exposure to flavor enhancers like MSG could influence gut health — especially in individuals who already struggle with digestive issues or inflammation.
Given the central role of the gut in overall health, including immune balance and neurochemical signaling, these findings deserve careful attention. PMC
Headaches and Neurological Symptoms
Many people report experiencing headaches, facial pressure, flushing or a general sense of discomfort after consuming foods high in MSG. These symptoms are often grouped under what is known as the “MSG symptom complex.” Harvard Health
While large placebo-controlled studies suggest that MSG does not cause symptoms in the general population, smaller studies and clinical observations indicate that a subset of individuals appears to be more sensitive, particularly when MSG is consumed in higher doses or on an empty stomach.
The exact mechanism remains unclear, but theories include glutamate’s role as an excitatory neurotransmitter and its interaction with the nervous system in susceptible individuals. PMC+1
MSG, the Immune System and Skin Reactions
Although the main review article does not focus on skin health, additional scientific literature suggests that MSG may, in rare cases, trigger immune-mediated or pseudo-allergic reactions affecting the skin.
Several case reports describe urticaria (hives), angioedema and facial swelling following MSG ingestion, confirmed through oral challenge tests and skin testing. Pubmed
In one documented case, a true Type I food allergy to MSG was identified — a finding that challenges the long-held assumption that MSG cannot provoke allergic responses. dovepress
That said, epidemiological studies confirm that true allergic reactions to MSG are extremely rare, affecting fewer than 1% of patients with chronic urticaria.
Still, for individuals with existing immune sensitivity, histamine intolerance or a compromised gut barrier, MSG may act as a trigger rather than a primary cause. PMC
What This Means for the Skin-Gut Axis
From a skin-gut-axis perspective, these findings are highly relevant. The gut microbiome, immune signaling and nervous system are deeply interconnected. Substances that disrupt gut balance may indirectly influence skin inflammation, barrier function and immune reactivity, even if the skin is not the primary target.
For most people, MSG consumption is unlikely to cause problems. However, if you notice recurring symptoms — such as headaches, digestive discomfort or unexplained skin flare-ups — after eating foods containing E621, it may be worth paying closer attention.
Conclusion
MSG (E621) is considered safe for the majority of the population. However, scientific evidence suggests that:
Some individuals may experience headaches or neurological symptoms after consuming MSG. Harvard Health
MSG can influence gut microbiota composition, with potential downstream effects on immune and metabolic health. PMC
Skin and immune reactions are rare but documented, particularly in sensitive individuals. doveexpress
Listening to your body, reading ingredient labels and experimenting with short elimination periods can offer valuable insights — especially if you are already navigating gut or skin challenges.
Marcelline Goyen BSc Skin Therapy
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